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Effect of Drug–Polymer Interaction in Amorphous Solid Dispersion on the Physical Stability and Dissolution of Drugs: The Case of Alpha-Mangostin
Improving drug solubility is necessary for formulations of poorly water-soluble drugs, especially for oral administration. Amorphous solid dispersions (ASDs) are widely used in the pharmaceutical industry to improve the physical stability and solubility of drugs. Therefore, this study aims to charac...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10384849/ https://www.ncbi.nlm.nih.gov/pubmed/37514423 http://dx.doi.org/10.3390/polym15143034 |
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author | Budiman, Arif Nurani, Neng Vera Laelasari, Eli Muchtaridi, Muchtaridi Sriwidodo, Sriwidodo Aulifa, Diah Lia |
author_facet | Budiman, Arif Nurani, Neng Vera Laelasari, Eli Muchtaridi, Muchtaridi Sriwidodo, Sriwidodo Aulifa, Diah Lia |
author_sort | Budiman, Arif |
collection | PubMed |
description | Improving drug solubility is necessary for formulations of poorly water-soluble drugs, especially for oral administration. Amorphous solid dispersions (ASDs) are widely used in the pharmaceutical industry to improve the physical stability and solubility of drugs. Therefore, this study aims to characterize interaction between a drug and polymer in ASD, as well as evaluate the impact on the physical stability and dissolution of alpha-mangostin (AM). AM was used as a model of a poorly water-soluble drug, while polyvinylpyrrolidone (PVP) and eudragit were used as polymers. The amorphization of AM-eudragit and AM-PVP was confirmed as having a halo pattern with powder X-ray diffraction measurements and the absence of an AM melting peak in the differential scanning calorimetry (DSC) curve. The solubility of amorphous AM increased in the presence of either eudragit or PVP due to amorphization and interactions of AM-polymer. Furthermore, FT-IR spectroscopy and in silico studies revealed hydrogen bond interactions between the carbonyl group of AM and the proton of eudragit as well as PVP. AM-eudragit with a ratio of 1:1 recrystallized after 7 days of storage at 25 °C and 90% RH, while the AM-PVP 1:4 and 1:10 samples retained the X-ray halo patterns, even under humid conditions. In a dissolution test, the presence of polymer in ASD significantly improved the dissolution profile due to the intermolecular interaction of AM-polymer. AM-eudragit 1:4 maintained AM supersaturation for a longer time compared to the 1:1 sample. However, a high supersaturation was not achieved in AM-PVP 1:10 due to the formation of large agglomerations, leading to a slow dissolution rate. Based on the results, interaction of AM-polymer in ASD can significantly improve the pharmaceutical properties of AM including the physical stability and dissolution. |
format | Online Article Text |
id | pubmed-10384849 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103848492023-07-30 Effect of Drug–Polymer Interaction in Amorphous Solid Dispersion on the Physical Stability and Dissolution of Drugs: The Case of Alpha-Mangostin Budiman, Arif Nurani, Neng Vera Laelasari, Eli Muchtaridi, Muchtaridi Sriwidodo, Sriwidodo Aulifa, Diah Lia Polymers (Basel) Article Improving drug solubility is necessary for formulations of poorly water-soluble drugs, especially for oral administration. Amorphous solid dispersions (ASDs) are widely used in the pharmaceutical industry to improve the physical stability and solubility of drugs. Therefore, this study aims to characterize interaction between a drug and polymer in ASD, as well as evaluate the impact on the physical stability and dissolution of alpha-mangostin (AM). AM was used as a model of a poorly water-soluble drug, while polyvinylpyrrolidone (PVP) and eudragit were used as polymers. The amorphization of AM-eudragit and AM-PVP was confirmed as having a halo pattern with powder X-ray diffraction measurements and the absence of an AM melting peak in the differential scanning calorimetry (DSC) curve. The solubility of amorphous AM increased in the presence of either eudragit or PVP due to amorphization and interactions of AM-polymer. Furthermore, FT-IR spectroscopy and in silico studies revealed hydrogen bond interactions between the carbonyl group of AM and the proton of eudragit as well as PVP. AM-eudragit with a ratio of 1:1 recrystallized after 7 days of storage at 25 °C and 90% RH, while the AM-PVP 1:4 and 1:10 samples retained the X-ray halo patterns, even under humid conditions. In a dissolution test, the presence of polymer in ASD significantly improved the dissolution profile due to the intermolecular interaction of AM-polymer. AM-eudragit 1:4 maintained AM supersaturation for a longer time compared to the 1:1 sample. However, a high supersaturation was not achieved in AM-PVP 1:10 due to the formation of large agglomerations, leading to a slow dissolution rate. Based on the results, interaction of AM-polymer in ASD can significantly improve the pharmaceutical properties of AM including the physical stability and dissolution. MDPI 2023-07-13 /pmc/articles/PMC10384849/ /pubmed/37514423 http://dx.doi.org/10.3390/polym15143034 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Budiman, Arif Nurani, Neng Vera Laelasari, Eli Muchtaridi, Muchtaridi Sriwidodo, Sriwidodo Aulifa, Diah Lia Effect of Drug–Polymer Interaction in Amorphous Solid Dispersion on the Physical Stability and Dissolution of Drugs: The Case of Alpha-Mangostin |
title | Effect of Drug–Polymer Interaction in Amorphous Solid Dispersion on the Physical Stability and Dissolution of Drugs: The Case of Alpha-Mangostin |
title_full | Effect of Drug–Polymer Interaction in Amorphous Solid Dispersion on the Physical Stability and Dissolution of Drugs: The Case of Alpha-Mangostin |
title_fullStr | Effect of Drug–Polymer Interaction in Amorphous Solid Dispersion on the Physical Stability and Dissolution of Drugs: The Case of Alpha-Mangostin |
title_full_unstemmed | Effect of Drug–Polymer Interaction in Amorphous Solid Dispersion on the Physical Stability and Dissolution of Drugs: The Case of Alpha-Mangostin |
title_short | Effect of Drug–Polymer Interaction in Amorphous Solid Dispersion on the Physical Stability and Dissolution of Drugs: The Case of Alpha-Mangostin |
title_sort | effect of drug–polymer interaction in amorphous solid dispersion on the physical stability and dissolution of drugs: the case of alpha-mangostin |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10384849/ https://www.ncbi.nlm.nih.gov/pubmed/37514423 http://dx.doi.org/10.3390/polym15143034 |
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